Mass spectrometers have become common tools in chemical analysis. Generally, mass spectrometers operate by separating ionized atoms or molecules based on differences in their mass-to-charge ratio (m/e). A variety of mass spectrometer devices are commonly in use, including ion traps, quadrupole mass filters, and magnetic sector mass analyzers.
The general stages in performing a mass-spectrometric analysis are: (1) create gas-phase ions from a sample; (2) separate the ions in space or time based on their mass-to-charge ratio; and (3) measure the quantity of ions of each selected mass-to-charge ratio. Thus, in general, a mass spectrometer system consists of an ion source, a mass-selective analyzer, and an ion detector. In the mass-selective analyzer, magnetic and electric fields may be used, either separately or in combination, to separate the ions based on their mass-to-charge ratio. Hereinafter, the mass-selective analyzer portion of a mass spectrometer system will simply be called a mass spectrometer. Ions introduced into a mass spectrometer are separated in a vacuum environment. Accordingly, it is necessary to prepare the sample undergoing analysis for introduction into this environment. This presents particular problems for high molecular weight compounds or other sample materials which are difficult to volatilize. While liquid chromatography is well suited to separate a liquid sample matrix into its constituent components, it is difficult to introduce the output of a liquid chromatograph (LC) into the vacuum environment of a mass spectrometer. One technique that has been used for this purpose is the electrospray method.
The "electrospray" or "electrospray ionization" technique is used to produce gas-phase ions from a liquid sample matrix to permit introduction of the sample into a mass spectrometer. It is thus useful for providing an interface between a liquid chromatograph and a mass spectrometer. In the electrospray method, the liquid sample to be analyzed is pumped through a capillary tube or needle. A high electrical potential (typically, 3 to 4 thousand volts) is established between the end of the needle and an opposing wall or other structure. The stream of liquid issuing from the needle tip is broken up into highly charged drops by the electric field, forming the electrospray. An inert gas, such as dry nitrogen (for example), may also be introduced through a surrounding capillary to enhance nebulization (droplet formation) of the fluid stream.
The electrospray drops consist of sample compounds in a carrier liquid and are electrically charged by the electric potential as they exit the capillary needle. The charged drops are transported in an electric field and injected into the mass spectrometer, which is maintained at a high vacuum. Through the combined effects of a drying gas and vacuum, the carrier liquid in the drops starts to evaporate giving rise to smaller, increasingly unstable drops from which surface ions are liberated into the vacuum for analysis. The desolvated ions pass through a sample aperture and ion lenses, and are focused into the high vacuum region of the mass spectrometer, where they are separated according to mass-to-charge ratio and detected by an appropriate detector (e.g., a photo-multiplier tube). In addition to, or in place of an electrostatic ion lens, a multipole RF ion guide may be used to transport the ions to the mass spectrometer.
Although the electrospray method is very useful for analyzing high molecular weight dissolved samples, it does have some limitations. For example, commercially available electrospray devices are limited to liquid flow rates of less than 20-30 microliters/min. Higher liquid flow rates result in unstable and inefficient ionization of the dissolved sample. Since the electrospray needle is typically connected to a liquid chromatograph, this acts as a limitation on the flow from the chromatograph.
One method of improving the performance of electrospray devices at higher liquid flow rates is to utilize a pneumatically assisted electrospray needle. One example of such a needle is formed from two concentric, capillary tubes. In such a device the sample containing liquid flows through the inner tube and a nebulizing gas flows through the annular space between the two tubes. This improves the efficiency of the ionization process by improving the ability of the electrospray needle to form drops from the sample liquid. However, at high sample liquid flow rates into this type of electrospray needle, the drops formed are relatively large and can degrade the performance of the mass spectrometer (by increasing the noise) if allowed to enter the device. This makes such electrospray needles difficult to use with liquid chromatographs.
As noted, large charged drops entering a mass spectrometer degrade its performance, and it is therefore desirable to eliminate or reduce the size of these drops. One mechanism to accomplish this is to employ electrostatic dispersion of drops, which occurs when coulomb forces exceed those due to surface tension. It is known that the surface tension is reduced by reducing the drop size through evaporation. As the drop size is reduced, the relative effect of the coulomb forces increases, causing the drops to spontaneously break up into smaller drops. Evaporation of the carrier liquid(s) from the drops permits the effect of the coulomb force to dominate that of the surface tension, with the benefit of decreasing the system noise of the mass spectrometer.
Thus, one way of reducing the noise problem caused by the larger drops produced by an electrospray needle is to employ means to reduce droplet size prior to injection into the mass spectrometer. One method of accomplishing this is shown in the prior art electrospray mass spectrometer interface 100 of FIG. 1. As shown in the figure, a liquid sample matrix flows through electrospray needle 102 and out of the needle's outlet, causing the liquid to form drops which are directed towards entrance orifice 104 of a mass spectrometer. A laminar flow of heated inert gas 106 is formed in a direction substantially counter to that of the flow from the outlet of needle 102, with the heated drying gas placed between the outlet of the electrospray needle and capillary tube 108 which serves as the entrance to the mass spectrometer 109. The heated inert gas facilitates evaporation of the solvent from the liquid drops, reducing their size, and acts to displace vapor formed from the evaporation process away from the entrance to the mass spectrometer. This is intended to reduce excess noise in the measurements made by the mass spectrometer.
In another prior art electrospray mass spectrometer interface 120 shown in FIG. 2, a drying gas 122 is arranged to flow in a transverse direction relative to entrance orifice 124 of the mass spectrometer. In addition, the direction of the sprayed drops produced by electrospray needle 126 is oriented at an angle off of the axis of the orifice. A second flow of heated drying gas 128, in a direction different from that of drying gas 122, intersects the droplet flow from needle 126 in a region upstream of the orifice (i.e., to the right of the orifice in the figure). Gas flows 122 and 128 mix, with the second flow 128 helping to evaporate the drops to produce ions and move the evaporating drops and ions toward the spectrometer orifice.
The prior art devices shown in FIGS. 1 and 2 have the disadvantage of requiring a relatively large volume of drying gas flowing counter to the direction of movement of the electrospray drops (or at some angle with respect to the direction of motion of the drops). The drying gas removes the carrier liquid(s) from the smaller charged drops, but does not efficiently separate the larger drops from smaller ones. Large drops will not be completely desolvated by the time they reach the sampling aperture into the mass spectrometer, unless very large drying gas flows are used. However, such larger gas flow rates can impede transfer of the ions into the orifice of the mass spectrometer.
Another disadvantage of the prior art devices is the formation of salt deposits at the capillary inlet to the spectrometer when nonvolatile salts are present in the sample liquid matrix. This is a problem when using high liquid flow rates into the electrospray needle in combination with high nebulizing gas flows, as in the previously described prior art device formed from concentric tubes. The problem arises because large drops that reach the entrance orifice into the mass spectrometer carry with them dissolved nonvolatile salts.
What is desired is an apparatus which provides an improved method of removing carrier liquid(s) from charged liquid drops formed by electrospray ionization. It is further desired to provide a method to improve the transfer of charged sample ions formed by electrospray ionization into a mass spectrometer. It is also desired to provide a method of removing large, charged drops that form when high liquid flow rates are used with electrospray ionization, prior to the large drops entering the mass spectrometer.